ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

Diseases of the central nervous system have become a growing global health concern. At present， there are many adverse reactions in the treatment with Western medicine. In contrast， traditional Chinese medicine has shown unique efficacy and rich clinical practice accumulation in diseases of the central nervous system. As a traditional Chinese medicine， Bupleuri Radix has played an important role in the treatment of neurological diseases through multi-target regulation， multi-pathway intervention， and multi-pathway mechanism of action. In recent years， with the in-depth study of the pharmacological effects of Bupleuri Radix， it has been found that the active ingredients such as saikosaponin， baicalin， quercetin， and kaempferol in Bupleuri Radix can be used as the main material basis for the treatment of neurological diseases. The results of this study showed that in neurodegenerative diseases， active ingredients of Bupleuri Radix can inhibit β-amyloid （Aβ） deposition and abnormal phosphorylation of microtubule-associated protein （Tau protein） in Alzheimer's disease， regulate the nuclear factor-κB/nuclear factor E₂ related factor 2 （NF-κB/Nrf2） pathway to play the anti-inflammatory role， and alleviate α-Synuclein （α-Syn） aggregation and mitochondrial damage in Parkinson's disease. In epilepsy， depression， and cerebral ischemia， they can improve symptoms by regulating neurotransmitters， oxidative stress， and apoptosis pathways， and inhibit brain glioma proliferation. However， the mechanism of action has not been fully elucidated， and the complexity of compound components and poor blood-brain barrier penetration limit their clinical application. In the future， it is necessary to integrate multi-omics， network pharmacology， and nano-delivery technologies， focus on the optimization of active ingredient group compounds and the precise guidance of biomarkers， accelerate the development of innovative therapies for Alzheimer's disease， Parkinson's disease， and other diseases for laying a solid theoretical foundation for further development and application and inspiring new research ideas.

ObjectiveAbnormal lipids in neurons can cause the accumulation of α-synuclein（α-syn）. This study aimed to explore the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） mice using lipidomics combined with network pharmacology. MethodsMice were divided into the blank group， model group and ASH （45.5 mg·kg^-1） group. Motor ability was evaluated by pole climbing time and autonomous activity count； The oxidative stress indicators were detected by enzyme-linked immunosorbent assay （ELISA）. Lipid biomarkers in brain tissues were screened and identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and metabolic pathway analysis was conducted. The key targets of ASH for PD treatment were explored using network pharmacology. The Kyoto Encyclopedia of Genes and Genomes （KEGG） database was used for pathway enrichment analysis， and the "compound-reaction-enzyme-gene" network was constructed using the MetScape plugin. The protein expression levels of glutathione S-transferase P1 （GSTP1）， glutathione S-transferase Mu 2 （GSTM2）， prostaglandin peroxide synthase 1 （PTGS1）， prostaglandin peroxide synthase 2 （PTGS2）， and prostaglandin E synthase （PTGES） were validated by Western blot. ResultsCompared with the blank group， the model group showed significantly prolonged pole climbing time and reduced autonomous activity count （P<0.01）. Compared with the model group， the ASH group demonstrated significantly faster pole climbing and increased autonomous activity count （P<0.01）. The model group exhibited significantly decreased superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） levels， and increased malondialdehyde （MDA） level in brain tissues compared with the blank group （P<0.01）. The ASH group showed increased SOD and GSH-Px levels and decreased MDA level compared with the model group （P<0.05， P<0.01）. Lipidomics analysis identified 10 differential metabolites and 8 differential metabolic pathways. Network pharmacological analysis revealed 213 intersection targets between ASH components and PD， with KEGG enrichment involving the sphingolipid signaling pathway， lipid arteriosclerosis， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway， and hypoxia inducible factor-1（HIF-1） signaling pathway. Integrated lipidomics and network pharmacology analysis highlighted the central role of the arachidonic acid metabolic pathway. The Western blot results showed that ASH effectively up-regulated GSTP1， GSTM2， and PTGS1 protein expression， and down-regulated PTGS2 and PTGES protein expression. ConclusionASH can ameliorate behavioral deficits， exert antioxidant effects， regulate lipid differential metabolites and the arachidonic acid metabolic pathway， thereby exerting therapeutic effects in PD model mice.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

BACKGROUND:Adult stem cell therapy is one of the research hotspots in the field of peripheral nerve injury repair and regeneration.With excellent properties of mesenchymal stem cells such as high acquisition rate,wide source,and rapid proliferation,mesoderm have been regarded as the ideal source of adult stem cells,while ectoderm-derived adult stem cells,especially neural crest stem cells,have certain neurogenic properties and attract more and more attention from researchers. OBJECTIVE:To mainly review the role and mechanism of multifunctional adult stem cells from ectoderm and mesoderm in peripheral nerve injury repair and regeneration,so as to explore the research progress and application prospect of adult stem cells from different sources and discuss the potential application value of adult stem cell therapy and the problems to be solved in connection with clinical studies. METHODS:The first author searched the relevant articles published from December 2001 to February 2024 in PubMed and SinoMed by computer in February 2024.The Chinese and English search terms were"ectodermal stem cells,mesenchymal stem cells,peripheral nerve injury,repair,regeneration."Finally,69 articles were included and analyzed. RESULTS AND CONCLUSION:(1)Ectodermal adult stem cells have excellent differentiation and regeneration potential,especially epidermal neural crest stems cells,olfactory stem cells,and dental ectomesenchymal stem cells,which have certain neurogenic properties and can express neural specific markers in vitro.However,relevant clinical research needs to be accumulated.(2)There are many types of adult stem cells derived from mesoderm,which are easy to obtain and purify.Among them,the efficacy and safety of bone marrow mesenchymal stem cells and umbilical cord mesenchymal stem cells in the repair of peripheral nerve injury are supported by clinical trials;that is,they can improve sensory and motor nerve conduction and there are no complications and obvious adverse reactions in follow-up.The acquisition of bone marrow mesenchymal stem cells needs invasive surgery and requires the patient to match the donor bone marrow type,which limit the application to some extent.Although umbilical cord mesenchymal stem cells do not require invasive harvesting,their isolation is difficult and phenotypically unstable.(3)Adult stem cells derived from endoderm often fail to grow in vitro,so the possibility of clinical application is low.(4)In conclusion,bone marrow mesenchymal stem cells are still the first choice for adult stem cell therapy in the treatment of peripheral nerve injury,which is suitable for cases without surgical contraindications and meeting the matching requirements,followed by umbilical cord mesenchymal stem cells supplemented by improved isolation methods and advanced phenotypic stability strategies.(5)Dental ectomesenchymal stem cells and adipose-derived mesenchymal stem cells have high application potential and need to be further tested in clinical trials.Other adult stem cells derived from ectodermal and mesodermal layers have significant advantages in animal and cell experimental studies due to their excellent properties.

ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.

Polymyxin is an essential antibiotic for treating multidrug-resistant Gram-negative bacterial infections； however， its significant nephrotoxicity greatly limits its clinical application. To enhance its safety and improve patient outcomes， the study of novel biomarkers for the early prediction of polymyxin-associated acute kidney injury is critically important. Novel biomarkers， such as cystatin C， kidney injury molecule-1， neutrophil gelatinase-associated lipocalin， N-acetyl-β-glucosaminidase， β2- microglobulin， have shown obvious advantages in the early prediction of polymyxin-associated acute kidney injury. Compared to traditional biomarkers， these biomarkers can provide sensitive and specific diagnostic information in the early stages of kidney injury， helping to optimize individualized treatment plans and reduce clinical risks. However， the high cost of detection and complex operation still limit their clinical promotion. Future research should focus on optimizing the detection technology of new biomarkers， simplifying the operation process and reducing costs， while conducting multi-center， large-scale randomized controlled trials to systematically evaluate the sensitivity and specificity of various novel biomarkers， in order to promote their application in the field of prediction of renal injury in clinical practice.